Exploration du savoir écologique traditionnel atikamekw au sujet de la santé des animaux et de la sélection des prises dans un contexte de choix alimentaires

Pour la nation atikamekw, la préservation de la santé du territoire ancestral et la possibilité de se nourrir de ses ressources demeurent essentielles au maintien de la culture. Au cours du dernier siècle, ce territoire a été l'objet de plusieurs perturbations en lien notamment aux aménagements hydroélectriques et aux activités reliées à l'exploitation forestière. Ces transformations, ainsi que la contamination qui peut en découler, ont entraîné des inquiétudes au sein des communautés atikamekw concernant la santé des animaux et la sécurité des aliments traditionnels. En 2004, un programme de recherche a été mis sur pied afin de proposer des solutions permettant le maintien de l'alimentation traditionnelle tout en minimisant les risques de contamination. L'étude exploratoire dont il est question dans ce mémoire s'insère dans ce projet. Elle visait plus précisément à documenter les changements qui ont été observés chez les animaux par les chasseurs et les pêcheurs atikamekw, les raisons qui selon eux expliquent ces changements, ainsi que les indicateurs qui leur permettent de déterminer si une prise est propre à la consommation ou non. Afin de recueillir ce savoir, quatre groupes de discussion, regroupant un total de 36 détenteurs de savoir, ont été réalisés dans les communautés d'Opitciwan et de Manawan à l'été 2008. Les Atikamekw possèdent un savoir écologique traditionnel (SET) qui comprend non seulement des observations concernant le milieu naturel, mais aussi des croyances, des valeurs et un code éthique. Ce savoir leur permet notamment de distinguer les changements qui résultent de variations naturelles de l'environnement, de ceux, plus inquiétants, qui sont causés par des perturbations anthropiques. Afin de déterminer si une prise est comestible, les chasseurs et les pêcheurs utilisent un ensemble d'indicateurs ayant trait à l'aspect physique de l'animal, mais aussi à son comportement et à son alimentation. Ces indicateurs sont interprétés au sein d'une vision de la santé qui accorde une place prépondérante au territoire. La documentation du savoir atikamekw a permis une meilleure compréhension de la perception de la problématique de la contamination de la nourriture traditionnelle par le peuple atikamekw, ainsi que ('identification de plusieurs facteurs intervenant dans les décisions à l'égard de la consommation d'aliments traditionnels. Ceux-ci pourront être intégrés dans l'élaboration de recommandations alimentaires culturellement pertinentes. \ud ______________________________________________________________________________ \ud MOTS-CLÉS DE L’AUTEUR : Atikamekw, savoir écologique traditionnel (SET), indicateurs de santé animale, choix alimentaires, santé des animau

Identification of Suicidal Ideation in the Canadian Community Health Survey—Mental Health Component Using Deep Learning

Introduction: Suicidal ideation (SI) is prevalent in the general population, and is a risk factor for suicide. Predicting which patients are likely to have SI remains challenging. Deep Learning (DL) may be a useful tool in this context, as it can be used to find patterns in complex, heterogeneous, and incomplete datasets. An automated screening system for SI could help prompt clinicians to be moreattentive to patients at risk for suicide.Methods: Using the Canadian Community Health Survey - Mental Health Component, we trained a DL model based on 23,859 survey responses to classify patients with and without SI. Models were created to classify both lifetime and last 12 month SI. From 582 possible parameters we produced 96 and 21 feature versions of the models. Models were trained using an undersampling procedure that balanced the training set between SI and non-SI; validation was done on held-out data.Results: For lifetime SI, the 96 feature model had an AUC of 0.79 and the 21 feature model had an AUC of 0.77. For SI in the last 12 months the 96 feature model had an AUC of 0.71 and the 21 feature model had an AUC of 0.68. In addition, sensitivity analyses demonstrated feature relationships in line with existing literature. Discussion: Although requiring further study to ensure clinical relevance and sample generalizability, this study is an initial proof of concept for the use of DL to improve identification of SI. Sensitivity analyses can help improve the interpretability of DL models. This kind of model would help start conversations with patients which could lead to improved care and a reduction in suicidal behavior

The Anti-Inflammatory Drug Leflunomide Is an Agonist of the Aryl Hydrocarbon Receptor

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the toxicity and biological activity of dioxins and related chemicals. The AhR influences a variety of processes involved in cellular growth and differentiation, and recent studies have suggested that the AhR is a potential target for immune-mediated diseases.During a screen for molecules that activate the AhR, leflunomide, an immunomodulatory drug presently used in the clinic for the treatment of rheumatoid arthritis, was identified as an AhR agonist. We aimed to determine whether any biological activity of leflunomide could be attributed to a previously unappreciated interaction with the AhR. The currently established mechanism of action of leflunomide involves its metabolism to A771726, possibly by cytochrome P450 enzymes, followed by inhibition of de novo pyrimidine biosynthesis by A771726. Our results demonstrate that leflunomide, but not its metabolite A771726, caused nuclear translocation of AhR into the nucleus and increased expression of AhR-responsive reporter genes and endogenous AhR target genes in an AhR-dependent manner. In silico Molecular Docking studies employing AhR ligand binding domain revealed favorable binding energy for leflunomide, but not for A771726. Further, leflunomide, but not A771726, inhibited in vivo epimorphic regeneration in a zebrafish model of tissue regeneration in an AhR-dependent manner. However, suppression of lymphocyte proliferation by leflunomide or A771726 was not dependent on AhR.These data reveal that leflunomide, an anti-inflammatory drug, is an agonist of the AhR. Our findings link AhR activation by leflunomide to inhibition of fin regeneration in zebrafish. Identification of alternative AhR agonists is a critical step in evaluating the AhR as a therapeutic target for the treatment of immune disorders

The Aryl Hydrocarbon Receptor Mediates Leflunomide- Induced Growth Inhibition of Melanoma Cells

A novel role of the dihydroorotatedehydrogenase (DHODH) inhibitor leflunomide as a potential anti-melanoma therapy was recently reported (Nature 471: 518-22, 2011). We previously reported that leflunomide strongly activates the transcriptional activity of the Aryl Hydrocarbon Receptor (AhR). We therefore tested whether the AhR regulates the anti-proliferative effects of leflunomide in melanoma. We first evaluated the expression of AhR in melanoma cells and found that AhR is highly expressed in A375 melanoma as well as in several other cancer cell types. To evaluate whether AhR plays a role in regulating the growth inhibitory effects of leflunomide in A375 cells, we generated a stable cell line from parental A375 cells expressing a doxycycline (DOX) inducible AhR shRNA. Using these cells in the absence or presence of DOX (normal AhR levels or AhR-knockdown, respectively) we found that the anti-proliferative effects of leflunomide, but not its metabolite A771726, were strongly dependent upon AhR expression. It has been well established that supplementation of cells with exogenous uridine completely rescues the anti-proliferative effects due to DHODH inhibition. Thus, we performed uridine rescue experiments in A375 cells to determine whether the anti-proliferative effects of leflunomide are solely due to DHODH inhibition as previously reported. Interestingly, saturating levels of uridine only modestly rescued A375 cells from the anti-proliferative effects of both leflunomide and A771726, indicating additional mechanism(s), apart from DHODH inhibition are responsible for the anti-proliferative effects of leflunomide in melanoma cells. Uridine also did not rescue MDA-MB-435S melanoma cell proliferation after leflunomide treatment. Our results reveal that the AhR is a molecular target of leflunomide and support the feasibility of the clinical application of leflunomide for treating melanoma. Furthermore, analysis of expression data from 967 cancer cell lines revealed that AhR is expressed in multiple different cancer types supporting the intriguing possibility of targeting the AhR for therapy in a number of cancers

Familial Autoimmune Thyroid Disease as a Risk Factor for Regression in Children with Autism Spectrum Disorder: A CPEA Study

A multicenter study of 308 children with Autism Spectrum Disorder (ASD) was conducted through the Collaborative Programs of Excellence in Autism (CPEA), sponsored by the National Institute of Child Health and Human Development, to compare the family history of autoimmune disorders in children with ASD with and without a history of regression. A history of regression was determined from the results of the Autism Diagnostic Interview-Revised (ADI-R). Family history of autoimmune disorders was obtained by telephone interview. Regression was significantly associated with a family history of autoimmune disorders (adjusted OR=1.89; 95% CI: 1.17, 3.10). The only specific autoimmune disorder found to be associated with regression was autoimmune thyroid disease (adjusted OR=2.09; 95% CI: 1.28, 3.41).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43035/1/10803_2005_Article_71.pd

Réflexion sur l’utilisation de groupes de discussion comme outil de documentation du savoir écologique traditionnel

La documentation du savoir traditionnel constitue souvent un passage obligé dans tout processus visant sa prise en compte et son intégration dans un cadre de recherche. La réalisation de groupes de discussion représente l’une des méthodes d’entrevue semi-dirigée les plus utilisées pour accomplir cette tâche. Plusieurs aspects de cette procédure sont discutés dans la littérature, mais peu d’auteurs ont abordé les défis supplémentaires d’une telle entreprise au sein d’une culture différente, par exemple chez les peuples autochtones. Cet article propose d’examiner ces défis à travers les différentes étapes de la documentation du savoir écologique traditionnel (SET) à la lumière de l’expérience acquise lors de la réalisation de quatre groupes de discussion au sein de deux communautés atikamekw du Québec (Canada). Il semble nécessaire de porter une attention particulière au contexte culturel afin d’adapter les méthodes utilisées tout au long du processus de documentation du savoir traditionnel, notamment à l’étape de l’analyse.Prior to the consideration and integration of traditional ecological knowledge, documentation is required. One of the most established semi-directed interview method to achieve this task is through focus groups. Many procedural aspects of this method have been discussed in the literature. However, few authors have addressed the additional challenges posed by conducting focus groups within an aboriginal community. The purpose of this paper is to examine these issues throughout the different stages of documenting traditional ecological knowledge, including the input of four focus groups conducted in two Atikamekw communities in Quebec, Canada. It is important to take into account the cultural context when conducting focus groups in order to tailor the research stages, primarily the analysis.

Revealing the complexity of community campus interactions

In this paper, four qualitative case studies capture the complex interplay between the social and structural relations that shape community - academic partnerships. Collaborations begin as relationships among people. They are sustained by institutional structures that recognize and support these relationships. Productive collaborations centralize reciprocity, flexibility, and relationship building between individuals and institutions. Our findings also indicate a synergistic interaction between collaborative processes and outcomes: an equitable process supports the development of mutually beneficial outcomes, and the ability to sustain a collaborative process requires substantive progress towards shared change goals

Santé territoriale, indicateurs de santé animale et vision holistique : La sélection des prises et les choix alimentaires chez les Atikamekw de Manawan et d’Obedjiwan

Dans le cadre d'un programme de recherche interdisciplinaire sur l'alimentation traditionnelle et les contaminants, des groupes de discussion ont été réalisés à l'été 2008 auprès des communautés atikamekw d'Obed jiwan et de Manawan (Québec) afin de documenter les changements qu'elles ont observés chez les animaux chassés et pêchés et d'obtenir une meilleure compréhension de leur processus de sélection des prises propres à la consommation. Les Atikamekw utilisent une multitude d'indicateurs afin d'évaluer l'état de santé des animaux qu'ils consomment. Les changements observés sont interprétés de façon holistique au sein d'une vision de la santé qui accorde une place prépondérante au territoire. La sélection des prises s'insère de plus dans un ensemble de facteurs qui influencent les choix alimentaires des Atikamekw. La documentation de ce savoir est essentielle à l'élaboration de recomman dations alimentaires culturellement pertinentes.As part of a multidisciplinary research project on traditional food and contaminants, focus groups were conducted in the summer of 2008 at the Atikamekw communities of Opitciwan and Manawan (Québec). The objective was to address the changes Atikamekw people have noticed in the game and fish and to seek a better understanding of the way they select a catch that is fit for consumption. The Atikamekw seem to use many indicators to assess the state of health of the animals they consume. These indicators are based on a holistic vision of health integrated in the concept of health of the land. The decision regarding the edibility of a catch is only one of many aspects that play a role in the process of food choices for the Atikamekw. It is essential to take these aspects into account in the development of food recommendations that are culturally relevant.En el marco de un programa de investigación interdisciplinario sobre la alimentación tradicional y los contaminantes en el verano de 2008 se realizaron grupos de discusión cerca de las comunidades atikamekw de Obedjiwan y de Manawan (Québec) con el fin de documentar los cambios que ellas han observado en los animales cazados y pescados y de obtener una mejor comprensión de los procesos de selección de capturas para el consumo. Los Atikamekw utilizan una gran variedad de indicadores con el fin de evaluar el estado de salud de los animales que ellos consumen. Los cambios observados son interpretados de manera holística en el seno de una visión de la salud que otorga un lugar preponderante en el territorio. La selección de las capturas se apoya cada vez más en un conjunto de factores que influencian las elecciones alimentarias de los Atikamekw. La documentación de este conocimiento es esencial en la elaboración de recomendaciones alimentarias culturalmente pertinentes

Adopter une approche écosystémique : accepter de changer

La reconnaissance et l’intégration de différentes sources de savoirs sont de plus en plus recommandées lorsqu’il s’agit d’aborder des problèmes environnementaux complexes. Pour y parvenir, de nouvelles approches favorisant l’intégration de divers savoirs se sont développées. Parmi celles-ci, les approches écosystémiques de la santé, grâce à leur caractère participatif et transdisciplinaire, impliquent la rencontre de plusieurs acteurs possédant différentes perspectives et partageant un intérêt pour une question commune. Cette approche a été adoptée dans le cadre d’un projet de recherche visant à développer des solutions culturellement pertinentes face au risque de contamination pouvant découler de la consommation de nourriture traditionnelle chez les communautés atikamekw. Elle nous a permis de porter un regard sur notre science et de procéder à une remise en question de nos méthodes afin de parvenir à un dialogue entre les différents savoirs et à une meilleure compréhension des enjeux propres aux communautés.In order to address complex environmental problems, the recognition and integration of different sources of knowledge are often required. To do so, new approaches have been developed. The ecosystem approach to health is one such new way. It combines participatory research and transdisciplinarity and involves the meeting of multiple stakeholders that typically hold different perspectives but share a common interest. We used such an approach in the context of a research project aiming to find culturally relevant solutions to the issue of environmental contaminants and “traditional” food safety for the Atikamekw communities. It allowed us to question our scientific methods in order to maintain a dialogue between the different knowledge bases and reach a better understanding of the issue from the communities’ perspective

A Structural Switch between Agonist and Antagonist Bound Conformations for a Ligand-Optimized Model of the Human Aryl Hydrocarbon Receptor Ligand Binding Domain

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates the expression of a diverse group of genes. Exogenous AHR ligands include the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which is a potent agonist, and the synthetic AHR antagonist N-2-(1H-indol-3yl)ethyl)-9-isopropyl-2- (5-methylpyridin-3-yl)-9H-purin-6-amine (GNF351). As no experimentally determined structure of the ligand binding domain exists, homology models have been utilized for virtual ligand screening (VLS) to search for novel ligands. Here, we have developed an “agonist-optimized” homology model of the human AHR ligand binding domain, and this model aided in the discovery of two human AHR agonists by VLS. In addition, we performed molecular dynamics simulations of an agonist TCDD-bound and antagonist GNF351-bound version of this model in order to gain insights into the mechanics of the AHR ligand-binding pocket. These simulations identified residues 307–329 as a flexible segment of the AHR ligand pocket that adopts discrete conformations upon agonist or antagonist binding. This flexible segment of the AHR may act as a structural switch that determines the agonist or antagonist activity of a given AHR ligand